Mutación de osteogénesis imperfecta en células medulares. (Inglés)

NEW YORK (Reuters Health) Feb 20 - Using viral vectors, US researchers have been able to target and eliminate the dominant gene mutations found in mesenchymal stem cells from patients with osteogenesis imperfecta.

In theory, these cells could then be transplanted back into the patient for therapeutic benefit.

Osteogenesis imperfecta is caused by mutations in the COL1A1 and COL1A2 genes that govern type I collagen production. The most severe forms of the disorder arise from dominant mutations that disrupt the normal helical structure of collagen.

As reported in the February 20th issue of Science, Dr. David W. Russell, from the University of Washington in Seattle, and colleagues created adeno-associated virus vectors that were designed to disrupt exon 1 of the COL1A1 gene.

With this technique, called gene targeting, they were able to disrupt the dominant-negative mutant COL1A genes found in the stem cells of OI patients. Moreover, the treated cells showed improved collagen production in vitro and were able to generate bone when transplanted into mice.

"A major advantage of gene targeting is that random integration events can be avoided or minimized, which could prevent the development of malignancies by oncogene activation, as observed after treatment with integrating retroviral vectors," the authors conclude.